Reaktion #426885

Reaktionsgleichung

NaBH4

2-Ethylhexanoic acid

product

tert-butyl 3-fluoro-4,4-dihydroxypiperidine-1-carboxylate

benzylamine

hydride

→

cis/trans mixture

Ausbeute 80.0%

tert-butyl 4-(benzylamino)-3-fluoropiperidine-1-carboxylate

Ausbeute 80.0%

Lösungsmittel

DCE

water

DCE

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONvia addition funnel
2. 2
   Temperaturwhile cooling
3. 3
   Sonstigethe reaction in a water bath
4. 4
   workup.STIRRINGThe reaction was stirred at ambient temperature for 2 days
5. 5
   Einengenconcentrated in vacuo
6. 6
   Sonstigeto remove solvent
7. 7
   SonstigeThe residue was partitioned between EtOAc (300 mL)
8. 8
   workup.STIRRINGThe mixture was shaken
9. 9
   Sonstigethe layers separated
10. 10
    Waschenthe organic phase washed again with a saturated aqueous Na2CO3 solution (100 mL) and finally with brine (50 mL)
11. 11
    ExtraktionThe aqueous phases were extracted with CHCl3 (3×75 mL)
12. 12
    Trocknenthe organic phases were dried over Na2CO3
13. 13
    Filtrationfiltered
14. 14
    Einengenconcentrated
15. 15
    SonstigeThe crude product was purified by column chromatography (EtOAc/Hexane)

Vorschrift

To a slurry of NaBH4 (7.567 g, 200.0 mmol) in DCE (200 mL) was added 2-Ethylhexanoic acid (95.50 mL, 600.0 mmol) slowly over 30 minutes via addition funnel. The mixture was stirred at ambient temperature for 4 hours with venting to release H2. In a separate 1 L flask was added the product from Step B (23.53 g, 100 mmol), benzylamine (16.37 mL, 150.0 mmol) and DCE (400 mL). The hydride solution was then added via addition funnel to the mixture over 1 hours while cooling the reaction in a water bath. The reaction was stirred at ambient temperature for 2 days, then diluted with water (100 mL) and concentrated in vacuo to remove solvent. The residue was partitioned between EtOAc (300 mL) and a saturated aqueous Na2CO3 solution (2×75 mL). The mixture was shaken, the layers separated and the organic phase washed again with a saturated aqueous Na2CO3 solution (100 mL) and finally with brine (50 mL). The aqueous phases were extracted with CHCl3 (3×75 mL), and the organic phases were dried over Na2CO3, filtered and concentrated. The crude product was purified by column chromatography (EtOAc/Hexane) providing 19.55 g of the pure cis product and 5.0 g of a cis/trans mixture (80%).

Quelle